Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract

Brian Becknell, John David Spencer, Ashley R. Carpenter, Xi Chen, Aspinder Singh, Suzanne Ploeger, Jennifer Kline, Patrick Ellsworth, Birong Li, Ehrhardt Proksch, Andrew L. Schwaderer, David Hains, Sheryl S. Justice, Kirk M. McHugh

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1-/-) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1-/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.

Original languageEnglish (US)
Article numbere77714
JournalPLoS ONE
Volume8
Issue number10
DOIs
StatePublished - Oct 21 2013
Externally publishedYes

Fingerprint

uropathogenic Escherichia coli
Uropathogenic Escherichia coli
beta-Defensins
urinary tract
Urinary Tract
bladder
Escherichia coli
Urinary Bladder
anti-infective agents
mice
Urothelium
ureter
Ureter
Messenger RNA
Antimicrobial Cationic Peptides
mucosal immunity
cystitis
Escherichia coli Infections
Mucosal Immunity
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Becknell, B., Spencer, J. D., Carpenter, A. R., Chen, X., Singh, A., Ploeger, S., ... McHugh, K. M. (2013). Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract. PLoS ONE, 8(10), [e77714]. https://doi.org/10.1371/journal.pone.0077714

Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract. / Becknell, Brian; Spencer, John David; Carpenter, Ashley R.; Chen, Xi; Singh, Aspinder; Ploeger, Suzanne; Kline, Jennifer; Ellsworth, Patrick; Li, Birong; Proksch, Ehrhardt; Schwaderer, Andrew L.; Hains, David; Justice, Sheryl S.; McHugh, Kirk M.

In: PLoS ONE, Vol. 8, No. 10, e77714, 21.10.2013.

Research output: Contribution to journalArticle

Becknell, B, Spencer, JD, Carpenter, AR, Chen, X, Singh, A, Ploeger, S, Kline, J, Ellsworth, P, Li, B, Proksch, E, Schwaderer, AL, Hains, D, Justice, SS & McHugh, KM 2013, 'Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract', PLoS ONE, vol. 8, no. 10, e77714. https://doi.org/10.1371/journal.pone.0077714
Becknell B, Spencer JD, Carpenter AR, Chen X, Singh A, Ploeger S et al. Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract. PLoS ONE. 2013 Oct 21;8(10). e77714. https://doi.org/10.1371/journal.pone.0077714
Becknell, Brian ; Spencer, John David ; Carpenter, Ashley R. ; Chen, Xi ; Singh, Aspinder ; Ploeger, Suzanne ; Kline, Jennifer ; Ellsworth, Patrick ; Li, Birong ; Proksch, Ehrhardt ; Schwaderer, Andrew L. ; Hains, David ; Justice, Sheryl S. ; McHugh, Kirk M. / Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract. In: PLoS ONE. 2013 ; Vol. 8, No. 10.
@article{5cb51f4b3620467a994c1f9901590ae8,
title = "Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract",
abstract = "Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1-/-) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1-/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.",
author = "Brian Becknell and Spencer, {John David} and Carpenter, {Ashley R.} and Xi Chen and Aspinder Singh and Suzanne Ploeger and Jennifer Kline and Patrick Ellsworth and Birong Li and Ehrhardt Proksch and Schwaderer, {Andrew L.} and David Hains and Justice, {Sheryl S.} and McHugh, {Kirk M.}",
year = "2013",
month = "10",
day = "21",
doi = "10.1371/journal.pone.0077714",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract

AU - Becknell, Brian

AU - Spencer, John David

AU - Carpenter, Ashley R.

AU - Chen, Xi

AU - Singh, Aspinder

AU - Ploeger, Suzanne

AU - Kline, Jennifer

AU - Ellsworth, Patrick

AU - Li, Birong

AU - Proksch, Ehrhardt

AU - Schwaderer, Andrew L.

AU - Hains, David

AU - Justice, Sheryl S.

AU - McHugh, Kirk M.

PY - 2013/10/21

Y1 - 2013/10/21

N2 - Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1-/-) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1-/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.

AB - Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1-/-) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1-/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.

UR - http://www.scopus.com/inward/record.url?scp=84886927256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886927256&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0077714

DO - 10.1371/journal.pone.0077714

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e77714

ER -